Research team receives NCI grant to develop precision therapies that kill cancer cells

Breakthrough research uses high-throughput screening to identify and target specific cancer genes in patients

A research team headed by Fred Hutchinson Cancer Research Center scientists Christopher Kemp, Ph.D., and Carla Grandori, M.D., Ph.D., has received a $4 million grant from the National Cancer Institute to develop precision therapies that selectively kill cancer cells while sparing normal, healthy tissue.

Utilizing high-throughput screening and RNA interference to rapidly test thousands of genes in patient-derived tumor cells, the team's work will identify new genes to target that may be highly specific to that patient's tumor.

"Therapies that target specific genes represent the future of oncology treatments," said Kemp, a member of the Human Biology Division at Fred Hutch. "For the most part, cancer therapy hasn't changed over the past several decades. Today's standard treatment is still based on conventional chemotherapy, which attacks all the cells in the body in order to kill the cancer cells. We are pioneering a more precise method that will specifically target cancer cells while sparing the normal cells."

Until recently, the complexities of cancer genomes, the frequent development of drug resistance and the lack of suitable technology have limited the availability and clinical success of targeted therapies. However, using high-throughput screening rather than the traditional method of testing one gene at a time can accelerate the discovery process a thousand-fold, cutting years off the time required to discover new drug targets.

"Most cancer therapies are specific to neither the individual patient nor the relevant underlying molecular features of a particular cancer," said Grandori, a research associate member of the Human Biology Division at Fred Hutch. "Applying high-throughput screening on a larger scale will allow us to identify and precisely target the unique vulnerabilities of cancers and develop personalized treatments," she said.

Although targeted therapies already in the clinic show great promise to be effective without the devastating side effects of chemotherapy, the menu of such therapies is still very limited, Grandori said. "While there a dozen or two targeted therapies, there are more than 20,000 genes, potentially many of them representing future targeted therapies. We have pioneered a method to sort through these thousands of genes efficiently and rapidly in patient-derived cancer cells."

The research team will identify new classes of drug targets and identify patient stratification criteria to match patients to the right drug targets. Initially, the focus will be on the aggressive subtypes of head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma and triple-negative breast cancer. Plans to expand screening into ovarian and childhood cancer types are also in the works.

The team has already demonstrated success in the preclinical setting; two tumor types for which no effective therapies exist have responded well to novel drug treatments. Kemp and Grandori are hopeful that these studies will be the basis to start clinical trials next year.

"This is just the beginning. We anticipate that our discoveries will lead to the next generation of precision medicines, including novel rational combination therapies tailored to molecular types of cancer," Kemp said. "Working with a local 'dream team' of cancer researchers, oncologists and computational scientists at Fred Hutch, the University of Washington and Sage Bionetworks we hope to bring this breakthrough method out of the lab and into the doctor's office."

Source: Fred Hutchinson Cancer Research Center